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MicroRNA-101 Targets CXCL12-Mediated Akt and Snail Signaling Pathways to Inhibit Cellular Proliferation and Invasion in Papillary Thyroid Carcinoma

Fang Chen*, Dongqiang Yang, Yuhua Ru, Shan Cao*, Aishe Gao*

* Department of Pathophysiology, Henan University of Traditional Chinese Medicine, Zhengzhou, Henan, P.R. China
† Department of Infectious Diseases, Henan Provincial People’s Hospital, Zhengzhou, Henan, P.R. China
‡ Department of Medical Academy, Soochow University, Soochow, Jiangsu, P.R. China

Oncology Research 2019, 27(6), 691-701. https://doi.org/10.3727/096504018X15426763753594

Abstract

Escalating evidence suggests that microRNA-101 (miR-101) is implicated in the development and progression of various cancers, including papillary thyroid carcinoma (PTC). However, the biological function and molecular mechanisms of miR-101 in PTC are still unclear. In this study, we demonstrated that miR-101 expression was significantly decreased in PTC tissues and cell lines. Clinically, a low level of miR-101 was positively associated with advanced histological stages and lymph node and distant metastases. The expression of CXCL12 was negatively correlated with miR-101 level in PTC. CXCL12 was validated as a direct target of miR-101 in PTC cells. Functional experiments proved that miR-101 markedly reduced the proliferation, apoptosis escape, migration, and invasion of PTC cells. Moreover, CXCL12 restoration rescued the suppressive effects of miR-101 on PTC cells by activating Akt- and EMT-associated signaling pathways. Overall, miR-101 exerts oncostatic effects on PTC by downregulating CXCL12 and repressing its downstream Akt and Snail signaling pathways, suggesting that miR-101/CXCL12/Akt or Snail axis may serve as a potential therapeutic target for PTC.

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Chen, F., Yang, D., Ru, Y., Cao, S., Gao, A. (2019). MicroRNA-101 Targets CXCL12-Mediated Akt and Snail Signaling Pathways to Inhibit Cellular Proliferation and Invasion in Papillary Thyroid Carcinoma. Oncology Research, 27(6), 691–701.



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